Similar Clinical Improvement Rates Among Biologic Drug Classes in Crohn's Disease: Systematic Review and Meta-Regression.

We conducted a systematic review and metaregression of pivotal Crohn's disease trials to evaluate the rates of change in Crohn's Disease Activity Index scores in patients receiving biologic treatments. The speed of clinical improvement was similar among biologic drug classes.

Modeling Endoscopic Improvement after Induction Treatment With Mesalamine in Patients With Mild-to-Moderate Ulcerative Colitis.

BACKGROUND & AIMS: Endoscopic improvement is an important treatment target for mild-to-moderate ulcerative colitis (UC). However, early endoscopic evaluation is not always feasible. We aimed to develop a clinical decision support tool to discriminate patients who have achieved endoscopic improvement from those with more severe inflammation following mesalamine induction therapy. METHODS: We performed a post-hoc analysis of data from a phase 3 non-inferiority trial of 726 adults with mild-to-moderate UC treated with mesalamine. Multivariable logistic regression modeling determined associations between candidate variables and endoscopic improvement (Mayo endoscopic subscore=0-1 according to blinded central reading) at Week 8. Internal model validation was performed using bootstrap resampling. A clinical decision support tool was developed to stratify patients into low, intermediate, and high probability groups for endoscopic improvement. RESULTS: Variables associated with endoscopic improvement at Week 8 included 50% reduction in fecal calprotectin from baseline (odds ratio [OR] 2.64, 95% CI:, 1.81, 3.85), reduction in rectal bleeding (OR 1.79 per point reduction, 95% CI: 1.35, 2.39), and improvement in physician global assessment (OR 2.32 per point improvement, 95% CI: 1.88, 2.85). The baseline Geboes score (OR 0.74 per grade, 95% CI: 0.65, 0.85) and prolonged disease duration (OR 0.95 per year, 95% CI: 0.92, 0.98) were negatively associated with endoscopic improvement. This model strongly discriminated endoscopic improvement in the development dataset (area under the curve [AUC] 0.84, 95% CI: 0.81, 0.87) and during validation (AUC 0.83). CONCLUSIONS: We developed and validated a clinical decision support tool that has good discriminative performance for induction of endoscopic improvement in patients with mild-to-moderate UC treated with mesalamine. ClinicalTrials.gov Registration: NCT01903252.

Higher Postinduction Infliximab Concentrations Are Associated With Improved Clinical Outcomes in Fistulizing Crohn's Disease: An ACCENT-II Post Hoc Analysis.

INTRODUCTION: There are only limited data regarding the role of therapeutic drug monitoring in fistulizing Crohn's disease (CD). We investigated the association between both induction and maintenance serum infliximab concentrations and favorable therapeutic outcomes in patients with fistulizing CD. METHODS: This was a post hoc analysis of the ACCENT-II trial evaluating patients with fistulizing CD receiving induction (n = 282) and maintenance infliximab therapy (n = 139). Investigated therapeutic outcomes at both week 14 and week 54 included fistula response, complete fistula response, C-reactive protein (CRP) normalization (≤5 mg/L) in patients with an elevated baseline CRP, and a more stringent outcome of composite remission, defined as combined complete fistula response and CRP normalization. Associations between serum infliximab concentrations and outcomes were assessed by multivariable logistic regression models. RESULTS: Higher week 14 infliximab concentrations were independently associated with week 14 fistula response (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.02-1.32; P = 0.019), and composite remission (OR: 2.32; 95% CI: 1.55-3.49; P < 0.001). Higher week 14 infliximab concentrations were also independently associated with week 54 composite remission (OR: 2.05; 95% CI: 1.10-3.82; P = 0.023). Based on receiver operating characteristic curve analysis, week 14 infliximab concentrations thresholds with combined maximal sensitivity and specificity of ≥20.2 µg/mL at week 2, ≥15 µg/mL at week 6, and ≥7.2 µg/mL at week 14 were associated with week 14 composite remission. DISCUSSION: Higher post-induction infliximab concentrations are associated with early and long-term favorable therapeutic outcomes in patients with fistulizing CD.

Development and Validation of a Clinical Decision Support Tool That Incorporates Pharmacokinetic Data to Predict Endoscopic Healing in Patients Treated With Infliximab.

BACKGROUND & AIMS: Infliximab is an effective treatment for moderate to severe ulcerative colitis (UC). Little is known about patient-related factors that might be used to predict endoscopic healing with infliximab therapy. METHODS: We analyzed data from 484 patients included in the randomized trials of the effects of infliximab therapy for patients with UC (Active Ulcerative Colitis Trials [ACT]-1 and ACT-2). We used a 2-compartment population pharmacokinetic model to calculate baseline infliximab clearance. Two multivariable regression models were derived and validated for their ability to identify patients with endoscopic healing (Mayo endoscopic score, ≤1) at weeks 8 and 30, using only baseline variables. We developed a clinical decision support tool (CDST) and calculator to determine the probability of endoscopic healing in patients starting infliximab. RESULTS: Higher baseline infliximab clearance, stool frequency, and rectal bleeding scores were associated negatively with endoscopic healing at week 8. In the validation set, a CDST score of 9 points or fewer identified patients without endoscopic healing at week 8 with 82% sensitivity (95% CI, 76%-88%), whereas a CDST score of 16 points or more identified patients with endoscopic healing at week 8 with 87% specificity (95% CI, 81%-94%). Higher baseline infliximab clearance, stool frequency score, white blood cell count, and lower body weight were associated negatively with endoscopic healing at week 30. In the validation set, CDST scores of 17 points or fewer identified patients without endoscopic healing at week 30 with 90% sensitivity (95% CI, 85%-95%), whereas scores greater than 22 points identified patients with endoscopic healing at week 30 with 80% specificity (95% CI, 73%-87%). External validation models had a modest predictive value, with an area under of the curve of 0.67 (95% CI, 0.61-0.74). Patient-level probabilities of endoscopic healing at weeks 8 or 30 can be calculated online (www.premedibd.com). CONCLUSIONS: Using data from 2 clinical trials of patients receiving infliximab therapy for UC, we developed and validated the CDST, which uses data on infliximab clearance and baseline patient and disease measures to identify patients most likely to have endoscopic healing. This tool will facilitate therapy decision making and precision medicine.

Evaluating the optimum number of biopsies to assess histological inflammation in ulcerative colitis: a retrospective cohort study.

BACKGROUND: The optimal ulcerative colitis biopsy protocol is unclear. AIM: To evaluate the number of biopsies required to accurately assess microscopic disease activity in ulcerative colitis METHODS: Biopsies from patients with ≥4 rectosigmoid samples, and clinical and endoscopic data, were retrospectively obtained from a prospective biobank. Histology and endoscopic videos were read blindly. A 4-biopsy Robarts Histopathology Index (RHI) reference score, consisting of the worst item-level ratings from four biopsies, was compared to 1-, 2- and 3-biopsy estimates. Agreement was determined using bivariate errors-in-variable regression analysis (acceptance interval: ±8.25). Endoscopic activity and disease location subgroup analyses were also performed. RESULTS: Forty-six patients had ≥4 rectosigmoid biopsies available (N = 287). The 2-biopsy (tolerance interval: -7.66, 4.79) and 3-biopsy (tolerance interval: -4.86, 3.46) RHI scores demonstrated acceptable agreement with 4-biopsy scores. One-biopsy scores demonstrated unacceptable agreement (tolerance interval: -13.99, 7.78). Mean RHI scores using the 2-, 3- and 4-biopsy approaches were similar (6.1 ± 9.6 P = 0.36; 6.8 ± 10.5, P = 0.7; 7.5 ± 11.2), whereas the 1-biopsy estimate was lower (4.4 ± 8.1, P = 0.06). Histological remission rates were identical for the 2-, 3- and 4-biopsy methods (65.2%, P = 1.0). Subgroup analysis demonstrated that three biopsies were required in patients with endoscopically active disease. Sampling additional colonic locations yielded lower histological remission rates compared to rectosigmoid sampling alone (33.3% vs 61.9%, P = 0.1). CONCLUSIONS: A minimum of two - conservatively, three - biopsies are required to reliably assess disease activity in a single colonic segment using the RHI. Further studies are needed of endoscopically active patients and sampling locations. These results have implications for biopsy strategies in clinical trials and practice.

Response to Placebo, Measured by Endoscopic Evaluation of Crohn's Disease Activity, in a Pooled Analysis of Data From 5 Randomized Controlled Induction Trials.

BACKGROUND & AIMS: Endoscopy is used to measure activity of Crohn's disease (CD) and determine eligibility and outcomes of participants in randomized controlled trials of therapeutic agents. We aimed to estimate the rate of response to placebo in trials, based on endoscopic evaluation of CD activity, and identify factors that affect this response. METHODS: We collected patient-level data from randomized, double-blind, placebo-controlled trials of therapeutic agents for CD that included centrally-read endoscopic assessments with validated scoring indices. We analyzed data from induction trials of eldelumab, filgotinib, risankizumab, and ustekinumab (from 188 patients given placebo). The primary outcome was the rate of response to placebo, based on endoscopic assessment of CD activity (>50% reduction in the simple endoscopic score for CD). Rate of remission, based on endoscopic score, was a secondary outcome. Overall rates of response to placebo were calculated using the inverse variance-weighted average method and presented with 95% CIs. We performed a multi-variable meta-regression analysis to identify determinants of response to placebo, assessed endoscopically, using patient-level data from the filgotinib and ustekinumab trials. RESULTS: The pooled rate of response among patients given placebo was 16.2% (95% CI, 10.5%-22.0%) and the rate of remission in this group was 5.2% (95% CI, 1.7%-8.8%). Prior exposure to tumor necrosis factor antagonists (odds ratio, 0.31; 95% CI, 0.10-0.93; P = .036) and increased concentration of C-reactive protein at baseline (odds ratio, 0.93; 95% CI, 0.87-0.98; P = .014 per 10 mg/L increase) were independently associated with lower rates of response to placebo. CONCLUSIONS: Rates of response and remission to placebo, determined by centrally-read endoscopy, in induction trials of therapies for CD are low. These estimates are important for sample size calculations for randomized placebo-controlled trials that use the Simple Endoscopic Score for CD as an endpoint. They also provide a benchmark to interpret findings from non-placebo controlled, prospective, randomized, unblinded trials.

Influence function-based empirical likelihood for inference of quantile medical costs with censored data.

In this paper, we propose empirical likelihood methods based on influence function and Jackknife techniques to construct confidence intervals for quantile medical costs with censored data. We show that the influence function-based empirical log-likelihood ratio statistic for the quantile medical cost has a standard Chi-square distribution as its asymptotic distribution. Simulation studies are conducted to compare coverage probabilities and interval lengths of the proposed empirical likelihood confidence intervals with the existing normal approximation-based confidence intervals for quantile medical costs. The proposed methods are observed to have better finite-sample performances than existing methods. The new methods are also illustrated through a real example.

Declining hospitalisation and surgical intervention rates in patients with Crohn's disease: a population-based cohort.

BACKGROUND: Lifetime risk of surgery in patients with Crohn's disease remains high. AIM: To assess population-level markers of Crohn's disease (CD) in the era of biological therapy. METHODS: Population-based cohort study using administrative data from Ontario, Canada including 45 235 prevalent patients in the Ontario Crohn's and Colitis Cohort (OCCC) from 1 April 2003 to 31 March 2014. RESULTS: CD-related hospitalisations declined 32.4% from 2003 to 2014 from 154/1000 (95% confidence interval (CI) [150, 159]) patients to 104/1000 (95% CI [101, 107]) (P < .001). There was a 39.6% decline in in-patient surgeries from 53/1000 (95% CI [50, 55]) to 32/1000 (95% CI [30, 34]) from 2003 to 2014 (P < .001). In-patient surgeries were mostly bowel resections. Out-patient surgeries increased from 8/1000 (95% CI [7, 9]) patients to 12/1000 (95% CI [10, 13]) (P < .001). Out-patient surgeries were largely related to fistulas and perianal disease and for stricture dilations/stricturoplasty. CD-related emergency department (ED) visits declined 28.4% from 141/1000 (95% CI [137, 146]) cases to 101/1000 (95% CI [99, 104]) from 2003 to 2014 (P < .001). Over the same time, patients receiving government drug benefits received infliximab or adalimumab at a combined rate of 2.2% in 2003 which increased to 18.8% of eligible patients by 2014. CONCLUSIONS: Rates of hospitalisations, ED visits and in-patient surgeries markedly declined in Ontario over the study period, while rates of biologic medication use increased markedly for those receiving public drug benefits.

Evaluation of optimal biopsy location for assessment of histological activity, transcriptomic and immunohistochemical analyses in patients with active Crohn's disease.

BACKGROUND: The appropriate location for biopsy procurement relative to an ulcer in active Crohn's disease is unknown. AIM: To explore the relationship between biopsy location, histological disease activity, proinflammatory gene expression and the presence of inflammatory cells. METHODS: Fifty-one patients with Crohn's disease and ulcers >0.5 cm diameter in the colon and/or ileum were prospectively enrolled at three centres. Biopsies were obtained from 0 mm, 7 to 8 mm and 21 to 24 mm from the edge of the largest ulcer. Histological activity was blindly assessed with the Global Histological Disease Activity Score, the Robarts Histopathology and Nancy Histological indices. Messenger ribonucleic acid (mRNA) levels for interleukins-6, -8 and -23 (p19 and p40 subunits), CD31 and S100A9 were measured using quantitative polymerase chain reaction. The number of CD3+, CD68+ and myeloperoxidase-positive cells was quantified by immunohistochemistry. Data were analysed using mixed models with location and segment as fixed effects and patients as random effect to account for correlation among segments within a patient. RESULTS: Histological disease activity scores (P < 0.0001), proinflammatory gene expression levels (P < 0.005) and numbers of myeloperoxidase-positive cells (P < 0.0001) were highest in biopsies from the ulcer edge in the colon and ileum, with decreasing gradients observed with distance from the edge (P < 0.05). No differences between colonic and ileal samples were detected for the parameters measured at any location. CONCLUSIONS: Biopsies from the ulcer edge in patients with Crohn's disease yielded the greatest histological disease activity and mRNA levels and had similar readouts in the colon and ileum. Research is needed to confirm this conclusion for other measures.

Infliximab Exposure-Response Relationship and Thresholds Associated With Endoscopic Healing in Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Therapeutic drug monitoring might be used to personalize infliximab treatment of patients with ulcerative colitis (UC), although exposure thresholds associated with endoscopic healing are uncertain. We aimed to determine infliximab concentration thresholds associated with endoscopic outcomes during induction and maintenance therapy for patients with UC. METHODS: We analyzed data from 484 patients with active UC included in 2 randomized controlled trials of infliximab vs placebo. Mayo endoscopic scores (MES) were available from weeks 0, 8, and 30. A 2-compartment population pharmacokinetic model was used to calculate infliximab clearance at baseline. We tested the linear trend between baseline infliximab clearance and MES at week 8. Receiver operating curve analysis identified infliximab clearance and concentration thresholds with a maximum Youden index corresponding to a MES of 0 or ≤1. RESULTS: We found a linear relationship between baseline infliximab clearance and week 8 MES (P < .001); a threshold of <0.397 L/d was associated with week 8 MES ≤1. Infliximab concentrations ≥18.6 µg/mL at week 2, ≥10.6 µg/mL at week 6, and ≥34.9 µg/mL at week 8 were associated with a week 8 MES of ≤1. Infliximab concentrations ≥5.1 µg/mL at week 14 and ≥2.3 µg/mL at week 30 were associated with a week 30 MES of ≤1. Infliximab concentrations ≥6.7 µg/mL at week 14 and ≥3.8 µg/mL at week 30 were associated with a week 30 MES of 0. CONCLUSIONS: Baseline clearance of infliximab and drug concentrations during induction and maintenance infliximab therapy are associated with short- and long-term endoscopic healing. Interventional studies that incorporate individualized dosing based on these parameters are required to show improved patient outcomes.

Varicella Vaccination Among US Adolescents: Coverage and Missed Opportunities, 2007-2014.

CONTEXT: Since 2007, 2 doses of varicella vaccine have been routinely recommended, with a catch-up second dose recommended for those who received only 1 prior dose. OBJECTIVE: To examine varicella vaccination coverage with 2 or more doses and the proportions of adolescents with evidence of immunity to varicella (≥2 doses of vaccine or varicella history) during 2007-2014. To assess timing of second-dose receipt, factors associated with 2 or more vaccine doses, and missed second-dose opportunities during 2014. DESIGN, SETTING, AND PARTICIPANTS: We used data from the 2007-2014 National Immunization Survey-Teen (NIS-Teen), which collects information on adolescents aged 13 to 17 years in the United States. RESULTS: From 2007 to 2014, varicella vaccination coverage with 2 or more doses increased from 8.3% to 66.9% in 13- to 15-year-olds and from 3.6% to 56.7% in 16- to 17-year-olds. The proportions with evidence of immunity also increased from 68.0% to 84.1% (13- to 15-year-olds) and 78.6% to 83.4% (16- to 17-year-olds). In 2014, 13.4% of 13- to 15-year-olds and 3.2% of 16- to 17-year-olds had received their second dose at 4 to 6 years of age. Factors most significantly associated with lower coverage with 2 or more doses were not having an 11- to 12-year well-child visit, not receiving an adolescent vaccine, and residence in a state with no 2-dose immunization school entry requirement. Seventy-seven percent of 1-dose vaccinated adolescents had 1 or more missed opportunities to receive their second dose; if were they not missed, 2-dose coverage would have increased from 79.5% to 94.8%. CONCLUSIONS: Levels of varicella vaccination coverage with 2 or more doses and the proportion of adolescents with evidence of immunity increased from 2007 to 2014, though 16% lacked evidence of immunity in 2014. Although catch-up campaigns have succeeded, missed vaccination opportunities persist.

A composite disease activity index for early drug development in ulcerative colitis: development and validation of the UC-100 score.

BACKGROUND: Combining clinical, endoscopic, and histological data associated with ulcerative colitis disease activity in a composite index could be a more sensitive way to detect efficacy in small numbers of patients during early drug development. Our aim was to derive and externally validate a novel index for this purpose. METHODS: Index development was done with data from a phase 2 placebo-controlled trial of ozanimod in patients with moderate-to-severe ulcerative colitis (n=179). Multivariable logistic regression modelling determined associations between candidate index items and absence of rectal bleeding (Mayo Clinic rectal bleeding subscore of 0), with items with a p value of less than 0·10 being taken forward into the final model. Model fit was internally validated and then externally validated in an independent phase 2 clinical trial dataset (MLN02, n=146) by measuring the area under the curve of the receiver operating characteristic (AUROC). FINDINGS: In the derivation cohort, multivariable analysis indicated that the Mayo Clinic stool frequency subscore (odds ratio [OR] 0·43, 95% CI 0·30-0·61; p<0·0001) and the Robarts histopathology index (0·97, 0·93-1·01; p=0·09) were associated with absence of rectal bleeding. Although the Mayo Clinic endoscopic subscore was not significantly associated with rectal bleeding in multivariable analysis (0·74, 0·43-1·27; p=0·27), it was entered into the final model on the basis of the established diagnostic and prognostic significance of endoscopic findings. With these parameters, we established the composite UC-100 score (1 + 16 × Mayo Clinic stool frequency subscore [0 to 3] + 6 × Mayo Clinic endoscopic subscore [0 to 3] + 1 × Robarts histopathology index score [0 to 33]), which ranges from 1 (no disease activity) to 100 (severe disease activity). The UC-100 score strongly discriminated absence of rectal bleeding in both the development (AUROC 0·82, 95% CI 0·75-0·88) and validation cohorts (0·86, 0·80-0·92). A UC-100 score of 25 or less corresponds to a 95% probability of absence of rectal bleeding. INTERPRETATION: We have developed and validated a novel composite disease activity index (the UC-100 score) with good discriminative performance that could used in early phase trials of ulcerative colitis. FUNDING: None.

Association of Health Insurance Status and Vaccination Coverage among Adolescents 13-17 Years of Age.

OBJECTIVE: To assess selected vaccination coverage among adolescents by health insurance status and other access-to-care characteristics. STUDY DESIGN: The 2015 National Immunization Survey-Teen data were used to assess vaccination coverage disparities among adolescents by health insurance status and other access-to-care variables. Multivariable logistic regression analysis and a predictive marginal modeling were conducted to evaluate associations between health insurance status and vaccination coverage. RESULTS: Overall, vaccination coverage was significantly lower among uninsured compared with insured adolescents for all vaccines assessed for except ≥3 doses of human papillomavirus vaccine (HPV) among male adolescents. Among adolescents 13-17 years of age, vaccination of uninsured compared with insured adolescents, respectively, for tetanus toxoid, reduced content diphtheria toxoid, and acellular pertussis vaccine was 77.4% vs 86.8%; for ≥1 dose of meningococcal conjugate vaccine was 72.9% vs 81.7%; for ≥1 dose of HPV was 38.8% vs 50.2% among male and 42.9% vs 63.8% among female adolescents; for 3 doses of HPV was 24.9% vs 42.8% among female adolescents. In addition, vaccination coverage differed by the following: type of insurance among insured adolescents, having a well-child visit at 11-12 years of age, and number of healthcare provider contacts in the past year. Uninsured were less likely than insured adolescents to be vaccinated for HPV (female: ≥1 dose and 3 doses; and male: ≥1 doses) after adjusting for confounding variables. CONCLUSIONS: Overall, vaccination coverage was lower among uninsured adolescents. HPV vaccination coverage was lower than tetanus toxoid, reduced content diphtheria toxoid, and acellular pertussis vaccine Tdap and meningococcal conjugate vaccine in both insured and uninsured adolescents. Wider implementation of effective evidence-based strategies is needed to help improve vaccination coverage among adolescents, particularly for those who are uninsured. Limitation of current federally funded vaccination programs or access to healthcare would be expected to erode vaccine coverage of adolescents.

Centrally Determined Standardization of Flow Cytometry Methods Reduces Interlaboratory Variation in a Prospective Multicenter Study.

OBJECTIVES: Flow cytometry (FC) aids in characterization of cellular and molecular factors involved in pathologic immune responses. Although FC has potential to facilitate early drug development in inflammatory bowel disease, interlaboratory variability limits its use in multicenter trials. Standardization of methods may address this limitation. We compared variability in FC-aided quantitation of T-cell responses across international laboratories using three analytical strategies. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from three healthy donors, stimulated with phorbol 12-myristate 13-acetate and ionomycin at a central laboratory, fixed, frozen, and shipped to seven international laboratories. Permeabilization and staining was performed in triplicate at each laboratory using a common protocol and centrally provided reagents. Gating was performed using local gating with a local strategy (LGLS), local gating with a central strategy (LGCS), and central gating (CG). Median cell percentages were calculated across triplicates and donors, and reported for each condition and strategy. The coefficient of variation (CV) was calculated across laboratories. Between-strategy comparisons were made using a two-way analysis of variance adjusting for donor. RESULTS: Mean interlaboratory CV ranged from 1.8 to 102.1% depending on cell population and gating strategy (LGLS, 4.4-102.1%; LGCS, 10.9-65.6%; CG, 1.8-20.9%). Mean interlaboratory CV differed significantly across strategies and was consistently lower with CG. CONCLUSIONS: Central gating was the only strategy with mean CVs consistently lower than 25%, which is a proposed standard for pharmacodynamic and exploratory biomarker assays.

Empirical likelihood-based confidence intervals for mean medical cost with censored data.

In this paper, we propose empirical likelihood methods based on influence function and jackknife techniques for constructing confidence intervals for mean medical cost with censored data. We conduct a simulation study to compare the coverage probabilities and interval lengths of our proposed confidence intervals with that of the existing normal approximation-based confidence intervals and bootstrap confidence intervals. The proposed methods have better finite-sample performances than existing methods. Finally, we illustrate our proposed methods with a relevant example.

Impact of Provider Recommendation on Tdap Vaccination of Adolescents Aged 13-17 Years.

INTRODUCTION: Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination has been recommended for adolescents in the U.S. since 2006. Information on Tdap vaccination by provider recommendation is limited. The purpose of this study is to assess recent Tdap vaccination by provider recommendation status among adolescents aged 13-17 years. METHODS: The 2013 National Immunization Survey-Teen data (N=18,948) were analyzed in 2016 to assess national and state-specific Tdap vaccination coverage disparities among adolescents by provider recommendation status, and other demographic and access to care variables. Multivariable logistic regression analysis and predictive marginal modeling evaluated associations between Tdap vaccination and provider recommendation status and other factors among adolescents aged 13-17 years. RESULTS: Overall, only 56.9% of adolescents aged 13-17 years received a provider recommendation for Tdap. Coverage was significantly higher among adolescents with a provider recommendation (88.6%) compared with those without a provider recommendation (80.5%) (p<0.05). Multivariable logistic regression showed that characteristics independently associated with a higher likelihood of Tdap vaccination included receiving a provider recommendation, Hispanic ethnicity, having two to three physician contacts in the past 12 months, having one or two vaccination providers, and receiving vaccinations from more than one type of facility (p<0.05). CONCLUSIONS: Provider recommendations were significantly associated with Tdap vaccination among adolescents aged 13-17 years. However, 43% of parents of adolescents did not receive a provider recommendation. Evidence-based strategies such as standing orders and provider reminders alone or health systems interventions in combination should be taken to improve provider recommendation and Tdap vaccination coverage.

National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years - United States, 2015.

The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents aged 11-12 years routinely receive vaccines to prevent diseases, including human papillomavirus (HPV)-associated cancers, pertussis, and meningococcal disease (1). To assess vaccination coverage among adolescents in the United States, CDC analyzed data collected regarding 21,875 adolescents through the 2015 National Immunization Survey-Teen (NIS-Teen).* During 2014-2015, coverage among adolescents aged 13-17 years increased for each HPV vaccine dose among males, including ≥1 HPV vaccine dose (from 41.7% to 49.8%), and increased modestly for ≥1 HPV vaccine dose among females (from 60.0% to 62.8%) and ≥1 quadrivalent meningococcal conjugate vaccine (MenACWY) dose (from 79.3% to 81.3%). Coverage with ≥1 HPV vaccine dose was higher among adolescents living in households below the poverty level, compared with adolescents in households at or above the poverty level.(†) HPV vaccination coverage (≥1, ≥2, or ≥3 doses) increased in 28 states/local areas among males and in seven states among females. Despite limited progress, HPV vaccination coverage remained lower than MenACWY and tetanus, diphtheria, and acellular pertussis vaccine (Tdap) coverage, indicating continued missed opportunities for HPV-associated cancer prevention.

Comparing human papillomavirus vaccine knowledge and intentions among parents of boys and girls.

BACKGROUND/OBJECTIVE: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Previous research suggests some differences between male and female adolescents in correlates of vaccine receipt and reasons for non-vaccination; few studies examine both sexes together. This analysis assessed knowledge and attitudes related to HPV disease and vaccination, intention to vaccinate, and reasons for delayed vaccination or non-vaccination among parents of boys and girls 13-17 y old in 50 states, the District of Columbia, and selected local areas. METHODS: National Immunization Survey-Teen 2013 data were analyzed and gender differences examined. RESULTS: In this sample, adolescent boys were more likely than girls to be unvaccinated and less likely to have completed the HPV vaccination series (p < 0.005 for both). Parents of girls were more likely than parents of boys to report a provider recommendation for HPV vaccination (65.0% vs. 42.1%). Only 29% of girls' parents reported a provider recommendation to begin vaccination by 11-12 y old. Among unvaccinated teens, parental intention to vaccinate in the next 12 months did not differ by sex, but reasons for vaccination or non-vaccination did. Many parents do not know the recommended number of HPV doses. CONCLUSIONS: Gender differences in provider vaccination recommendations and reasons for vaccination might partially explain differential HPV uptake by male and female adolescents. Clinicians should offer strong recommendations for HPV vaccination at 11-12 y old for both girls and boys. To reduce missed opportunities, HPV vaccination should be presented in the context of, and given concurrently with, other routinely administered vaccines.

Human Papillomavirus Vaccination Coverage Among Girls Before 13 Years: A Birth Year Cohort Analysis of the National Immunization Survey-Teen, 2008-2013.

Routine human papillomavirus (HPV) vaccination is recommended at 11 or 12 years by the Advisory Committee on Immunization Practices. National Immunization Survey-Teen data were analyzed to evaluate, among girls, coverage with one or more doses of HPV vaccination, missed opportunities for HPV vaccination, and potential achievable coverage before 13 years. Results were stratified by birth year cohorts. HPV vaccination coverage before 13 years (≥1 HPV dose) increased from 28.4% for girls born in 1995 to 46.8% for girls born in 2000. Among girls born during 1999-2000 who had not received HPV vaccination before 13 years (57.2%), 80.1% had at least 1 missed opportunity to receive HPV vaccination before 13 years. Opportunities to vaccinate for HPV at age 11 to 12 years are missed. Strategies are needed to decrease these missed opportunities for HPV vaccination. This can be facilitated by the administration of all vaccines recommended for adolescents at the same visit.